Method and apparatus for measuring velocity of chromatographic pulse

ABSTRACT

An Apparatus and method for two-stage chromatographic separation uses thermal modulation. The chromatographic column or modulation tube ( 1 ) has a loop structure such that two portions of modulation tube ( 1 ) can be thermally modulated simultaneously by at least one thermal modulation device, which device can have a cold gas source, jet tube ( 2 ), and a hot gas source, hot jet tube ( 5 ), to modulate the temperature of the portions ( 3, 4 ) of modulation tube ( 1 ).

FIELD OF THE INVENTION

This invention relates to the field of gas chromatography.

BACKGROUND OF THE INVENTION

Prior Art Thermal Modulation

Thermal modulation is a means of producing chemical pulses of shortduration in capillary gas chromatographic columns.

Thermal modulators grew out of prior art ohmically heated cryogenictraps, which received attention in the scientific literature for someyears, following demonstration by Hopkins and Pretorious that ohmicheating of cryogenic traps was faster than the heating obtained with ahot gas stream. (B. J. Hopkins, and V. Pretorious, Journal ofChromatography, 158 (1978) 471). A number of ohmically heated singlestage thermal modulators were reported, examples of which are describedin the following publications, incorporated in their entireties hereinby reference:

-   -   1. J. Phillips, et al. “Thermal Desorption Modulation as a        Replacement for Sample Injection in Very-Small-Diameter Gas        Chromatography Capillary Columns”, Journal of Chromatographic        Science 1986, vol. 24, pp. 396-399.)    -   2. S. Springston. “Cryogenic-focussing, ohmically heated        on-column trap for capillary gas chromatography.” Journal of        Chromatography, 517 (1990) 67-75.    -   3. A. van Es, J. Janssen, C. Cramers, and J. Rijks. “Sample        Enrichment in High Speed Narrow Bore Capillary Gas        Chromatography”, Journal of High Resolution Chromatography and        Chromatography Communications, 11 (1988) 852-857.

Single stage modulators, such as those described in the abovepublications, were found to concentrate and release sample substances assharp chemical pulses, but suffered certain limitations. First, ohmicfilms having very low thermal inertia had to be overdriven in order toheat underlying capillary column segments having much higher thermalinertias. Overdriving caused ohmic coatings to burn out at unpredictabletimes. A further limitation of the above designs was undesirable tailingof the concentration pulses generated, which limited the utility of thedevices for sampling continuous, or semi-continuous sample streams, suchas the effluent of an analytical GC column.

The tailing observed with single stage thermal modulators was eliminatedby the two-stage thermal modulator introduced by Phillips and Liu, asdescribed in U.S. Pat. Nos. 5,135,549 and 5,196,039, and European PatentNo. 0522150, which are incorporated in their entireties herein.Two-stage thermal modulators produced sharp and symmetrical chemicalpulses by refocusing a chemical pulse emitted from a first modulatorstage at the head of a second thermal modulator stage downstream of thefirst. The two modulator stages are pulse-heated and cooled 180° out ofphase with one another, in order to achieve the refocusing effect. Thedevice proved its ability to sample semi-continuous sample streams in acapillary tube, such as the effluent from an analytical column. Thisfunctionality gave rise to the startling advance of comprehensivetwo-dimensional gas chromatography. As originally implemented, however,ohmically heated two-stage thermal modulators burned out frequently, andunpredictably, and were moreover difficult to prepare and handle.

Ledford and Phillips introduced a solution to the burnout problem, asdescribed in U.S. Pat. No. 6,007,602, which is incorporated in itentirety herein. Although their heater system was reliable, theirimplementation employed moving parts in the vicinity of the column,which made the device difficult to manufacture and handle in the field.A moving cooler system attributable to Marriott (see for example R. M.Kinghorn and P. J. Marriott, “Enhancement of Signal-to-Noise Ratios inCapillary Gas Chromatography by Using A Longitudinally ModulatedCryogenic System”, Journal of High Resolution Chromatography, 21 (1998)32-38) suffered similar disadvantages.

Ledford et al eliminated problems associated with moving parts in thevicinity of the column by introducing a two-stage thermal modulatoremploying pulsed heated and cooled gas jets, described in U.S.Provisional Patent Application No. 60/175,727, filed Jan. 12, 2000, andPCT application WO 01/51170 PCT/US01/01065, filed Jan. 12, 2001, whichare incorporated in their entireties herein by reference. The jetmodulator was relatively easy to manufacture and use, and producedexcellent thermal modulations, including the surprising ability tomodulate volatile substances, such as methane. The principle drawback ofthis design was the complexity of the apparatus, which employed fourvalves, a heat exchanger, and a bulky mechanical assembly forpositioning a modulator tube in the paths of pulsed hot and cold jets.

A variation of the jet modulator was introduced by Beens (J. Beens, etal. “Simple, non-moving modulation interface for comprehensivetwo-dimensional gas chromatography ”Journal of Chromatography A, 919 (1)(2001) pp. 127-132, which is incorporated in its entirety herein byreference.) Beens employed two high pressure valves to pulse jets ofliquid carbon dioxide onto two portions of a capillary tube in themanner known to effect two-stage thermal modulation. The jets wereseparated by about ten centimeters within the GC oven. Unlike the deviceof Ledford et al, Beens did not employ gas jets to heat the cooledstages of the modulator tube, but rather relied on the stirred oven bathof the gas chromatograph to heat the modulator stages. To this end,Beens positioned the column on a sprung metal bracket carryingconventional column fittings. This bracket tensioned the modulator tube,held it in the paths of the CO2 jets, and was an open structure thatexposed the modulator tube to the oven bath. When applied tocomprehensive two-dimensional gas chromatography, Beens's systemgenerated high quality GC×GC images.

Even with the admirable simplicity and good performance of the Beensdesign, certain limitations were encountered. First, liquid carbondioxide refrigerant employed in the cold jets produces jet gastemperatures of about −77° C., unsuitable for modulation of chemicalcompounds with volatilities greater than that of octane. This isproblematical for important samples such as gasoline and naptha, inwhich modulation over the C5+ range, or lower carbon numbers, isdesirable. Second, the carbon dioxide consumption rate of the jets washigh enough (c.a. 200 std. liters/min, semi-continuous) to pose safetyrisks in the event of ventilation failure in the room. Third, deadvolume between the valves and the jet nozzles could be cleared rapidlyonly at high gas flow rates. At low gas flow rates, it would bequestionable whether the dead volumes would clear rapidly enough topermit high quality thermal modulation. Thus the Beens device requiresfairly high gas flow rates through the cold jets. Fourth, high pressurevalves present risks to operators that low-pressure valves do not, andare moreover expensive. Fifth, carbon dioxide was admitted to themodulator tube by means of precision fabricated nozzles, which wereartful to construct. Sixth, the observed chemical pulse width generatedby the Beens device was on the order of 60 to 70 milliseconds, ascompared to 36 milliseconds with systems employing hot jet heating ofthe modulator stages. Narrow pulse widths are desirable in thermalmodulation, because well-focused chemical pulses translate to improvedsensitivity and resolution in gas chromatographic instruments. Seventh,permanent frost spots appeared on the capillary columns when the coldjets were pulsed at high frequencies, indicating that the heating rateprovided by an ambient oven limits the frequency at which the modulatorcould operate. High frequency modulation is desirable in someapplications, such as sensitivity enhancement of one-dimensional gaschromatography, or high speed GC×GC. Eighth, threading columns through apair of fittings doubled the work of installing columns into the GCoven.

Various embodiments of the prior art are taught, for example, in U.S.Pat. No. 5,135,549 to Phillips et al., printed on Aug. 4, 1992, U.S.Pat. No. 5,196,039 to Phillips et al., printed on Mar. 23, 1993, U.S.Pat. No. 6,007,602 to Ledford et al., printed on Dec. 28, 1999, and U.S.patent application Ser. No. 09/760,508 to Ledford et al., filed on Jan.12, 2001, which are hereby incorporated in their entireties byreference.

In view of various limitations of prior art thermal modulators, thisinventor believed that further innovation in jet modulator technologywas needed.

SUMMARY OF THE PRESENT INVENTION

The present invention is the result of several discoveries concerningthe nature and operation of jet modulators. This inventor has found:

-   Low-flow cold jets (10 std. liter per minute gas flow rate) are    capable of cooling a modulator stage located 3 millimeters away from    the jet outlet, even when the modulator stage is exposed to the    stirred oven bath of a gas chromatograph. This discovery simplified    mounting modulator tubes in the path of jets, which can now be done    with a cartridge structure having no column fittings.-   Jet modulators work significantly better with pulsed hot jets than    without.-   A high-flow hot jet can divert a low-flow cold jet away from the    modulator tube, thereby permitting the cold jet to be operated    continuously, rather than pulsed with a valve. This discovery led to    simplification of apparatus.-   By looping a modulator tube more than once through the path of a    cold jet, and heating the multiplicity of cold spots thus formed    with a single pulsed hot jet, multi-stage thermal modulation is    achieved with apparatus comprising a single low cost valve operated    at low pressure. This discovery further simplified apparatus.-   The so-called “loop modulator” permits in-situ measurement of the    velocity of a chemical substance within the body of a capillary    tube, as well as detailed characterization of the thermal modulation    process. These unanticipated benefits are particularly welcome: they    permit new methods for the study of physical and physico-chemical    processes in capillary tubes.

It is an object of the present invention to provide a novel method formulti-stage thermal modulation.

It is an object of the present invention to provide a novel apparatusfor multi-stage thermal modulation.

It is an object of the present invention to implement multi-stagethermal modulation with a single pulsed valve.

It is an object of the present invention to provide a novel means ofmeasuring the velocity of a chemical substance traveling through acapillary tube.

It is an object of the present invention to provide a capillary columnholder that is robust in its construction, and easy to use.

It is an object of the present invention to provide a multi-stagethermal modulator suitable for comprehensive two-dimensional gaschromatography (GC×GC).

It is an object of the present invention to provide a means formulti-stage thermal modulation that is sufficiently inexpensive,manufacturable, and easy to use, as to be a commercially viable productin the field of gas chromatography.

In accordance with these and other purposes of the invention, a methodof thermal modulation is provided whereby a single pulsed valve effectshigh quality multi-stage thermal modulation, and permits the velocity ofa chemical substance in a capillary tube sustaining a flow of carriergas to be measured.

Furthermore, apparatus is provided, comprising a retention alterationmeans, gas jet means, a modulator tube, and means for manipulating thetemperature of a modulator tube, said apparatus providing thermalmodulation of chemical substances admixed with a carrier gas and flowingthrough a tube.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be better understood with reference to theaccompanying drawings, which describe a “loop modulator” embodimentsatisfying the objects of invention.

FIG. 1 a is a side view of an embodiment of the present inventionshowing a cold gas jet tube, a hot gas jet tube, and a loop modulator;

FIG. 1 b is a front view of the embodiment shown in FIG. 1 a;

FIG. 2 depicts a detailed cross-sectional side view of the embodimentshown in FIG. 1 a;

FIG. 3 a is a top view of an embodiment of the present invention showinga first and a second modulator stage;

FIG. 3 b is a perspective view of the embodiment shown in FIG. 3 a;

FIG. 4 a is a cross-sectional side view of an embodiment of the presentinvention showing a heat exchanger;

FIG. 4 b is a cross-sectional side view of an embodiment of the presentinvention showing a source of the cold gas jet;

FIG. 5 a is a side view in partial phantom of an embodiment of thepresent invention depicting the gas flow of the cold gas jet;

FIG. 5 b is a side view in partial phantom of an embodiment of thepresent invention showing the interaction of the cold gas jet and thehot gas jet;

FIG. 6 is a graphical representation of the peak height and spacing of asample that has been processed by an embodiment of the presentinvention.

Other various embodiments of the present invention will be apparent tothose skilled in the art in consideration of the specification andpractice of the invention described herein, and the detailed descriptionthat follows. It is intended that the specification and examples beconsidered as exemplary only, and that the true scope and spirit of theinvention includes those other various embodiments.

DETAILED DESCRIPTION OF THE INVENTION

The present invention can be further described in terms of the followingmethods and apparatus:

A method, herein referred to as method “A,” comprises a method ofthermal modulation for generating chemical pulses in a fluid streamflowing through a modulator tube, said method comprising the steps of:

-   -   a. providing a modulator tube comprising an inlet, a first        portion in communication with said inlet, a second portion in        communication with said first portion, and an outlet portion in        communication with said second portion;    -   b. creating a fluid stream in a direction through the modulator        tube to produce a carrier fluid stream;    -   c. introducing a sample into the carrier fluid stream, said        sample comprising one or more chemical substances;    -   d. manipulating the temperature of the first portion to cause at        least a portion of the sample to be retained therein;    -   e. manipulating the temperature of the second portion such that        at least a portion of the sample will be retained therein;    -   f. accumulating a sample component in the first portion for a        period of time to form a first concentration, the accumulated        sample component being carried into the first portion by the        carrier fluid stream;    -   g. manipulating the temperature of the first portion to release        the first concentration into the carrier fluid stream in the        form of a first chemical pulse;    -   h. causing the first chemical pulse to be carried in the        direction of the carrier fluid stream flow toward the second        portion;    -   i. accumulating the first chemical pulse in said outlet portion        so as to focus and hold the first chemical pulse therein for a        period of time and form a second concentration which is more        compact in distance than the first chemical pulse, sample        components of the first chemical pulse being carried to the        outlet portion by the carrier fluid stream;    -   j. manipulating the temperature of the first portion to        accumulate at least one second sample component therein for a        period of time, the at least one second sample component being        carried into the first portion by the carrier fluid stream;    -   k. manipulating the temperature of the second portion so as to        release the second concentration into the carrier fluid stream        in the form of an outlet chemical pulse, the outlet chemical        pulse being of shorter duration than the first chemical pulse;    -   l. manipulating the temperature of the second portion such that        a subsequent chemical pulse is retained therein; and        -   wherein travel of a first concentration from the first            portion to the second portion in step (h) is delayed such            that:        -   steps (d), (e), (j) and (l) may occur simultaneously during            an interval of time; and        -   steps (g) and (k) may occur simultaneously during an            interval of time.

The present invention provides method “A,” wherein the modulator tubeincludes a portion that is shaped in the form of a loop.

The present invention provides method “A,” wherein steps (d), (e), (j),(l), (g), and (k) are effected within a single thermal manipulationzone.

The present invention provides method “A,” wherein a first portion and asecond portion are formed by passing said tube more than once throughsaid single thermal manipulation zone, such that a delay loop betweensaid first portion and said second portion is formed.

The present invention provides method “A,” wherein said thermalmanipulation zone comprises a stream of cooled gas.

The present invention provides method “A,” wherein said stream of cooledgas is pulsed.

The present invention provides method “A,” wherein said thermalmanipulation zone comprises a stream of heated gas.

The present invention provides method “A,” wherein said stream of heatedgas deflects a stream of cooled gas.

The present invention provides method “A,” further comprising the stepsof:

-   -   m. measuring the time of travel of a concentration of a sample        substance through said delay loop;    -   n. measuring the length of said delay loop; and    -   o. calculating the velocity of said concentration of sample        substance through said delay loop.

The present invention provides method “A,” further comprisingdetermining a van't Hoff plot for a sample substance.

The present invention provides method “A,” wherein said modulator tubeis part of a one-dimensional gas chromatograph.

A thermal modulation apparatus is provided, referred to herein asapparatus “B,” for generating chemical pulses in a fluid stream flowingthrough a modulator tube, said apparatus comprising:

a modulator tube having an inlet, a first portion which is a length ofsaid tube in communication with said inlet, a second portion which is alength of said tube in communication with said first portion, and anoutlet portion in communication with said second portion;

a means for creating a fluid stream in a direction through saidmodulator tube to produce a carrier fluid stream;

a means for introducing a sample comprising one or more samplecomponents into the carrier fluid stream;

a means for manipulating the temperature of the first portion to causeat least a portion of the sample to be retained therein;

a means for manipulating the temperature of the second portion such thatthe one or more components will be retained therein;

a means for accumulating a sample component in the first portion for aperiod of time to form a first concentration of sample, the accumulatedsample substance being carried into the first portion by the carrierfluid stream;

a means for manipulating the temperature of the first portion to releasethe first concentration into the carrier fluid stream in the form of afirst chemical pulse;

a means for causing the first chemical pulse to be carried in thedirection of carrier fluid stream flow toward the second portion;

a means for accumulating the first chemical pulse in said outlet portionso as to focus and hold the first chemical pulse therein for a period oftime and form a second concentration of sample which is more compact indistance than the first chemical pulse, sample substances of the firstchemical pulse being carried to the outlet portion by the carrier fluidstream;

a means for manipulating the temperature of the first portion toaccumulate more sample substance therein for a period of time, thesample substance being carried into the first portion by the carrierfluid stream;

a means for manipulating the temperature of the second portion so as torelease the second concentration into the carrier flow stream in theform of an outlet chemical pulse, the outlet chemical pulse being ofshorter duration than the first chemical pulse;

a means for manipulating the temperature of the second portion such thata subsequent chemical pulse is retained therein; and

a means for delaying the travel of the first chemical pulse to thesecond portion, such that the temperatures of the first and secondportions can be manipulated simultaneously.

Apparatus “B” is provided wherein said means for manipulating thetemperature of the first portion to release the first concentration intothe carrier fluid stream comprises a retention alteration means.

Apparatus “B” is provided wherein said means for manipulating thetemperature of the first portion to release the first concentration intothe carrier fluid stream comprises a stream of heated gas directed ontothe first portion.

Apparatus “B” is provided wherein said means for manipulating thetemperature of the second portion to release the second concentrationinto the carrier fluid stream comprises a retention alteration means.

Apparatus “B” is provided wherein said means for manipulating thetemperature of the second portion to release the second concentrationinto the carrier fluid stream comprises a stream of heated gas directedonto the second portion.

Apparatus “B” is provided, said apparatus further comprising means formeasuring the velocity of a chemical pulse between the first portion andthe second portion.

Apparatus “B” is provided, said apparatus further comprising means forconstructing a van't Hoff plot.

Apparatus “B” is provided, said apparatus further comprising means forpredicting the velocity of a chemical substance in a tube.

Apparatus “B” is provided for increasing the sensitivity of aone-dimensional gas chromatograph.

Apparatus “B” is provided wherein means for manipulating the temperatureof a first portion and a second portion comprise a single pulsed streamof gas.

A thermal modulation apparatus, referred to herein as apparatus “C,” isalso provided for generating chemical pulses in a fluid stream flowingthrough a modulator tube, said apparatus comprising:

a modulator tube having an inlet, a first portion in communication withsaid inlet at a first portion inlet, a second portion in communicationwith said first portion at a second portion inlet, and an outlet portionin communication with said second portion, wherein at least a portion ofthe modulator tube is formed in a loop such that the first portion inletport and the second portion inlet are adjacent one another such thatthey can be thermally modulated simultaneously with a single thermalmodulating device;

an inlet port for introducing a sample comprising one or more samplecomponents into a carrier fluid stream flowing through the modulatortube; and

at least one thermal modulating device adapted to direct at least onestream of heated gas, cooled gas, or both heated gas and cooled gas,toward said first and second inlet portions simultaneously.

The apparatus “C” is provided, further comprising a carrier fluid streamflowing through the modulator tube.

Another thermal modulation apparatus is provided according to theinvention for generating chemical pulses in a fluid stream flowingthrough a modulator tube, said apparatus comprising:

a modulator tube having an inlet, a first portion in communication withsaid inlet, a second portion in communication with said first portion,and an outlet portion in communication with said second portion;

a fluid stream in a direction through said modulator tube to produce acarrier fluid stream;

an injection port for introducing a sample comprising one or more samplecomponents into the carrier fluid stream; and

a thermal modulator that is adapted to:

-   -   manipulate the temperature of the first portion to cause at        least a portion of the sample to be retained therein;    -   manipulate the temperature of the second portion such that        sample will be retained therein;    -   accumulate a sample component in the first portion for a period        of time to form a first concentration of sample, the accumulated        sample component being carried into the first portion by the        carrier fluid stream;    -   manipulate the temperature of the first portion to release the        first concentration into the carrier fluid stream in the form of        a first chemical pulse;    -   cause the first chemical pulse to be carried in the direction of        carrier fluid stream flow toward the second portion;    -   accumulate the first chemical pulse in said outlet portion so as        to focus and hold the first chemical pulse therein for a period        of time and form a second concentration of sample which is more        compact in distance than the first chemical pulse, sample        components of the first chemical pulse being carried to the        outlet portion by the carrier fluid stream;    -   manipulate the temperature of the first portion to accumulate a        second sample component therein for a period of time, the second        sample component being carried into the first portion by the        carrier fluid stream as an additional chemical pulse;    -   manipulate the temperature of the second portion so as to        release the second concentration into the carrier flow stream in        the form of an outlet chemical pulse, the outlet chemical pulse        being of shorter duration than the first chemical pulse;    -   manipulate the temperature of the second portion such that a        subsequent chemical pulse is retained therein; and    -   delay the travel of the first chemical pulse to the second        portion, such that the temperatures of the first and second        portions containing the additional chemical pulse and the second        chemical pulse, respectively, can be manipulated simultaneously.

FIGS. 1 a and 1 b show a schematic of the loop modulator in side and endviews, respectively. A length of tubing, the modulator tube 1, sustainsa flow of carrier gas, and is coiled so as to pass twice through thepath of a jet tube 2 conducting cold gas to a first portion of themodulator tube 3, and simultaneously to a second portion of themodulator tube 4, thereby forming the first and second stages,respectively, of a two-stage thermal modulator. Disposed at right anglesto the cold jet is a hot jet tube 5 sustaining a flow of gas pulsed bymeans of an electronically controlled solenoid valve 6. The hot jet gasstream is heated by a heater block 7 carrying a cartridge heater 8. Inthe front view of the apparatus, the cold jet tube 2 partially eclipsesthe hot jet tube 5, and totally eclipses the cartridge heater 8. Thefront view makes it clear that the first modulator stage, i.e., thefirst modulator tube portion 3, is upstream, with respect to carrier gasflow direction, of the second modulator stage, or second modulator tubeportion 4.

FIG. 2 depicts the mechanical structure of the loop modulator in moredetail. The cold jet tube 2 is enveloped in a vacuum jacket 9 evacuatedat a port 10 mounted in a machined bulkhead 11. The bulkhead 11, coldjet tube 2, and vacuum envelope 9 are secured together by silversoldered joints at 12. Disposed at right angles to the cold jet is thehot jet tube 5, heated by heater block 7 and cartridge heater 8. An RTDtemperature sensor 13, connected via cable 14, and electrical connector15 to a temperature control circuit (not shown), provides temperatureregulation of the heater block. The hot jet tube 5 is fastened to a gassupply tube 16 by means of a Swagelock union 17. The gas supply tubeconnects to a pulsed solenoid valve (not shown). The valve solenoid isactuated by the application of 24 Volt DC, controlled by a solid-staterelay, as is commonly known in electronic art. The valve is pulsed bymeans of a pulse generator board (Model 6602, National Instruments,Austin, Tex.), controlled by a software interface written in C++,according to instructions supplied by the manufacturer of the pulseboard.

The modulator tube 1 is housed in a column holder 18, which is insertedinto a slotted clamp 19, operated by a thumbscrew 20. The column holderengages the column clamp by friction, so that its position in theslotted clamp is easily adjustable. The vertical position of the clamp20 may be adjusted up and down, whereby the modulator stages may bepositioned in the path of the hot jet, or below the path of the hot jet.In either vertical position, the modulator stages remain in the path ofthe cold jet gas.

FIGS. 3 a and 3 b depict the column holder 18 as a rectangular sheet ofstainless steel with the edges folded on a bending brake, therebyforming a pair of “wings” 119 that hold the column 1 in place. The“wings” 119 are sprung so that they create friction drag when the columnholder 18 is inserted into the slotted clamp (not shown). Insertion ofthe column into the holder is a simple process. The modulator column iswound into a coil 20, which acts as a delay line, or delay loop, and isinserted into the folded metal wings 19, whereby the coil is captured inthe column holder. A first modulator stage 3 is constructed by pushingthe carrier input leader 21 toward the column holder 18, therebyextending a column winding toward the end of the column holder oppositethat of the carrier input leader. The second modulator stage 4 isconstructed in like manner by pushing the carrier output leader. Oncepositioned in the column holder 18, the modulator tube is tacked withpolyimide glue to prevent the coils and modulator stages from movingduring subsequent handling. As shown in FIG. 3 b, the column coil 20 andmodulator stages 3 and 4 spring toward the inner walls of the bent-overwings, such that the column suspends itself in the mid-plane of thecolumn holder.

If the hot jet is pulsed for a period of time shorter than the timerequired for the chemical pulse to travel around the delay loop 20, suchthat the cold spot on the downstream modulator stage 4 is re-establishedprior to the arrival of the chemical pulse, then the chemical pulse isaccumulated in the downstream modulator stage 4, thereby effectingtwo-stage thermal modulation.

Many methods exist for cooling the gas delivered to the cold jet. InFIGS. 4 a and 4 b, a method for producing a gas jet with a temperatureof −110° C. to −189° C. is indicated. A source of gaseous nitrogen 23directed through a pressure regulator 24 supplies a stream of gas to atube 25, which conveys the gas to a heat exchange coil 26 bathed in aliquid nitrogen bath 57. The latter is contained in a standardlaboratory dewar 28. The stream of nitrogen gas cools to near liquidnitrogen temperature in the heat exchange tube, and passes to the coldjet tube (not shown) via connecting tube 40, which is surrounded by aninsulation sheath 27. The sheath 27 may be made of plastic foam sleevingof the type commonly used to insulate household plumbing pipes, in whichcase, gas temperatures within the cold jet tube reach temperatures of−110° C. to −170° C., depending on the gas flow rate and the amount oftime the apparatus is allowed to cool. The insulation sheath 27 can alsobe a vacuum jacketed transfer line of the type commonly employed incryogenic art. In that case, jet gas temperature of −189° C. is readilyachieved. At this temperature, methane gas can be thermally modulated.

FIG. 4 b depicts cooling the jet with gaseous carbon dioxide withdrawnfrom the headspace of a valved liquid CO₂ cylinder 28. The CO₂ isconveyed through a steel (0.063 inch o.d., 0.030 inch i.d.) transfertube 29 at high pressure (c.a. 1,000 psi). The end of this transfer tube29 is crushed to restrict the flow rate of CO₂ gas exiting the tube toapproximately 10 standard liters per second. The work of expansion coolsthe CO₂ gas to about −77° C., suitable for thermal modulation across theC9+ carbon range.

It is also possible to direct-liquid CO₂ to a crushed tube restrictor,in which case the heat of vaporization must be supplied to the expandingliquid jet, in order to prevent the formation of dry ice in the cold jettube. One method of supplying the heat of vaporization is to admix theCO₂ with a stream of nitrogen “makeup” gas admitted to the cold jet tubevia a “tee” fitting, and controlled by means of a needle valve. It isfound that the temperature of the CO2/N₂ mixture exiting the jet tubecan be smoothly controlled by adjusting the needle valve over atemperature range from −85° C. to −40° C. At temperatures of −80° C. orbelow, microscopic dry ice particles form in the jet of gas exiting thecold jet tube. These particles scatter light, and permit the shape ofthe gas jet to be seen by the operator.

FIG. 5 illustrates the use of a liquid CO₂/N₂ jet, the temperature ofwhich was adjusted by means of a variable Nitrogen makeup flow to avalue at which dry ice formation made the cold jet visible. The cold jetwas found to be laminar, and exhibited the characteristic cone shape 30of a moving laminar column of gas equilibrating with a surrounding gasat a different temperature (candle effect). The portions of themodulator tube 20 immersed within this cold jet accumulated chemicalsubstances, i.e., functioned as thermal modulator stages in accumulationmode.

FIG. 5 b depicts the loop modulator in release mode. A “hot” jet 31comprised of room temperature gas (no power applied to the heater block)preserved dry ice particles in the jet, which permitted the operator toobserve that the cold jet was deflected away from the modulator stages 3and 4. When the hot jet heater block 7 was powered, such that the heaterblock temperature was maintained at about 100° C. or higher, the dry iceparticles in the cold jet disappeared the moment the jot jet fired.

Under thermal modulation conditions, if the operator places a fingerbelow the modulator tube, he or she can feel the cold jet disappear whenthe hot jet pulses—a simple demonstration of the jet deflection mode.This deflection mode is possible because low-flow cold jets are easilydiverted by high-flow hot jets. Deflection mode eliminates the need topulse the cold jets, as has been practiced in prior art jet modulators.The resulting simplification of apparatus is attributable to thediscovery that a low-flow cold jet can effectively cool a thermalmodulator stage even when exposed to turbulent air in a stirred ovenbath. (Prior art jet designs of Ledford et al had used low-flow coldjets that were shielded from the stirred oven bath by the column holderassembly).

It is useful to present sample substances, such as n-alkanes, to athermal modulator continuously, so as to monitor modulation pulsescontinuously while modulation parameters are varied. A simple way topresent sample continuously is to load a common 10 μl syringe with aliquid hydrocarbon, such as decane, insert the syringe needle into theGC injector, and leave it there. After an initial surge of samplematter, an exponential decay of the sample concentration is observed,which settles into a long tail of nearly constant amplitude, as samplematerial diffuses from the syringe into the GC injector. In this way, asteady stream of sample substance can be continuously presented to athermal modulator for many tens of minutes.

If, in the presence of continuously presented sample, the hot jet ispulsed on for a period of time longer than the time required for achemical pulse to traverse the delay loop, the accumulated contents ofboth modulator stages will be released. If the modulator tube isconnected to a GC detector, such as an FID, both released pulses can beobserved, as is apparent from FIG. 6.

In FIG. 6, the left-hand pulse 33 is the chemical pulse released fromthe second stage of the thermal modulator by the hot jet. It containsonly the amount of material present in the delay loop at the moment thecold spots in the modulator stages were established during the previoussample accumulation step (the delay loop “clears” into the secondmodulator stage shortly after the cold jet is turned on.) The right-handpulse 32 is the chemical pulse released from the first stage of thethermal modulator by the hot jet. It contains the amount of materialcontinuously accumulated throughout an entire thermal modulation cyclein the presence of a continuous sample stream, as described above.

The time difference Δt between the maxima of the two chemical pulsesreleased from the two modulator stages is the time required for thechemical pulse formed by the first modulator stage to travel around thedelay loop.

If the length, L, of the delay loop is known, then the ratio L/Δt is theaverage velocity, |u|, of the first chemical pulse in the delay loop.Because the length of the delay loop can be made very small compared tothe overall length of a capillary column, the average velocity |u|closely approximates the instantaneous velocity u(x) at the midpoint, x,of the delay loop. The velocities of both retained and unretainedsubstances within the body of the modulator tube can be measured in thisway.

The velocity of an unretained chemical substance is that of the carriergas, u₀. If both u for a chemical substance and u₀ for a carrier gas aremeasured in the manner described above, then the well known relationk=u/u ₀−1yields the partition coefficient k for a substance retained by themodulator tube. Determination of k, together with a knowledge of thecolumn phase ratio β, permit calculation of the free energy of solution,ΔG, of a given analyte on a given stationary phase coating on the innerwall of a modulator tube. Knowledge of the ΔG for a given analyte on agiven stationary phase permits the chromatographic behavior of thatanalyte to be predicted on any capillary column coated with thatstationary phase. Numerical prediction of gas chromatograms is thenpossible, as is numeric optimization of chromatographic conditions forsuch thermodynamically characterized analytes.

The ease with which the present invention permits in-situ velocitymeasurements within a capillary tube permits many quantitativeinvestigations of physical and physico-chemical processes in capillarycolumns that were not possible with prior gas chromatographic art. Forexample, measuring velocity at different positions along a capillarycolumn would permit an experimental velocity profile to be determined.Such a profile would facilitate quantitative tests of gas compressiontheory in capillary columns, gas chromatographic measurement ofthermodynamic properties of analytes, quantitative and experimentallyverifiable treatments of chemical pulse formation in thermal modulators,and tuning of secondary columns in GC×GC.

It is a surprising aspect of the present invention that in-situmeasurement of the velocity of a chemical vapor within the body of acapillary tube is so easily performed. In this, and other respects, thepresent invention is a novel scientific instrument.

Typical Operating Conditions and Results

Liquid Nitrogen Cooled Jets. Liquid nitrogen cooled jets producemodulation pulses of some 30 to 36 milliseconds duration (base of peak).Peaks as narrow as 24 milliseconds have been observed, narrower than anyobserved with prior art jet modulators.

Typical operating conditions for a liquid nitrogen cooled loop modulatorwould be:

Inlet Temperature: 250° C. Inlet Pressure: 20 psi Split Ratio: 300Carrier Gas: Hydrogen Modulation Period: 3 seconds Hot Jet Duration: 200ms Modulator Tube i.d. 0.1 mm Modulator Tube o.d. 0.2 mm ModulatorStationary Phase None (bare deactivated FSOT) Cold Jet Temperature:−130° C. Cold Jet Flow Rate: 5 standard liters per second OvenTemperature +35° C. Hot Jet Temperature +100° C. Delay Loop Length: 60cm Detector: FID Digitizing Frequency: 200 HzUnder these conditions, chemical pulses formed by thermal modulation ofpropane are 30 milliseconds wide at base. Organic substances in the C3+range modulate readily under the same conditions. Hexadecane exhibitsmodulation pulse widths of 48 ms at base. Modulation peaks aresymmetric. Holdup time in the modulator is greater than ten seconds.

Carbon Dioxide Cooled Jets. Carbon dioxide cooled jets are suitable formodulating organic substances in the C9+ range if CO₂ gas is employed asthe cold jet refrigerant, and over the C8+ range is CO₂ liquid isemployed as the cold jet refrigerant, on uncoated modulator tubes. Theuse of nitrogen makeup gas in the case of CO₂ liquid refrigerantprevents dry ice buildup in the cold jet tube, because the makeup gassupplies heat of vaporization to the expanding CO₂ jet.

Typical conditions for gaseous CO₂ modulation are:

Inlet Temperature: 250° C. Inlet Pressure: 20 psi Split Ratio: 300Carrier Gas: Hydrogen Modulation Period: 3 seconds Modulator Tube i.d.0.1 mm Modulator Tube o.d. 0.2 mm Modulator Stationary Phase None (baredeactivated FSOT) Cold Jet Temperature: −77° C. Cold Jet Flow Rate: 10standard liters per second Oven Temperature +120° C. Hot Jet Temperature+220° C. Hot Jet Duration: 100 ms Delay Loop Length: 60 cm Detector: FIDDigitizing Frequency: 200 HzUnder these conditions, decane exhibits symmetrical modulation pulses 36milliseconds wide at base.

Hot Jet vs. Ambient Oven Heating. By moving the column holder clamp upor down on the vacuum jacket of the cold jet, it is possible to positionthe modulator stages in or out of the path of the hot jet. In the lattercase, the modulator stages are heated by the stirred air bath in the GCoven. This experiment permits comparison of the two heating modes, hotjet vs. ambient oven, under identical modulation conditions. Under theconditions described above, for both liquid nitrogen and CO₂ cooled loopmodulators, ambient oven heating of modulator stages producedasymmetric, tailed peaks, 70 to 75 milliseconds wide at base fordodecane. Hot jet heating of modulator stages produced symmetric peaks30 to 36 milliseconds wide at base for dodecane. The asymmetry of theoven-heated peak consists of an exponential tail on the rising edge ofthe peak, which indicates sluggish release from the second stage of thethermal modulator. It should be noted that the release profile isfunctionally related to the acceleration of a chemical pulse.

In-Situ Velocity Measurement. If the duration of the hot jet pulse isextended to a value greater than the travel time of a chemical substancearound the delay loop, chemical pulses from both modulator stages arereleased from the loop. This permits velocity measurement, as describedabove, if the length of the delay loop is known. The velocitymeasurement can be conducted with or without stationary phase in themodulator tube.

The velocity measurements can be made in the presence of a full GC×GCcolumn set. In this case, some broadening of modulation pulses isexpected as a result of partitioning on the stationary phase of thesecondary column. However, the secondary column can have no effect onthe time difference between chemical pulses emitted from the first andsecond modulator tube stages. Because both pulses are composed of thesame chemical substance, both must have identical velocities on thesecondary column, under isothermal conditions, which preserves the timedifference between the chemical pulses, even though they traverse thestationary phase of a secondary column.

Typical conditions for a velocity measurement with a GC×GC column setinstalled in the gas chromatograph are:

Inlet Temperature: 250° C. Inlet Pressure: 20 psi Split Ratio: 300Carrier Gas: Hydrogen Sample: Butane, Continuous Modulation Period: 4seconds Modulator Tube i.d. 0.1 mm Modulator Tube o.d. 0.2 mm ModulatorStationary Phase None (bare deactivated FSOT) Cold Jet Temperature: −77°C. Cold Jet Flow Rate: 27 standard liters per second Oven Temperature+150° C. Hot Jet Temperature +250° C. Hot Jet Duration: 2000 ms DelayLoop Length: 65 cm Detector: FID Digitizing Frequency: 200 Hz PrimaryColumn: 10 meter long 0.1 mm i.d. Methylsilicone, 0.25μ film thicknessSecondary Column: 0.5 meter long 0.1 mm i.d. Carbowax, 0.1μ filmthicknessUnder these conditions, the modulation profile shown in FIG. 6 wasobtained, which exhibits features that cannot be observed with any priorart thermal modulation system.

In FIG. 6, a butane peak 32 released from the second stage of thethermal modulator is visible and distinguishable from a butane peak 33released from the first stage of the thermal modulator. The separationbetween the two butane peaks is 1200 ms. Because the modulator tube was0.65 meter long, the average velocity of the butane through the delayloop was 0.65 meter/1.2 second=0.54 meter/second.

Referring to FIG. 6, the chemical pulse 33 from the second stage of thethermal modulator has a more complex shape than the chemical pulse 32from the first stage. An initial surge in the peak intensity of thefirst stage chemical pulse is followed by a plateau, or “shelf” 34lasting 800 ms. This plateau is attributable to sample material gated tothe modulator by a hot jet pulsed on for 2000 msec. Note that the sum ofthe loop delay period and the duration of the plateau equals the hot jetduration (see parameters above). Clearly, the plateau is caused by thefact that sample from the injector was continuously presented to thecolumn (by leaving a loaded syringe in the GC injector). Once the firststage chemical pulse traverses the second stage of the modulator, thecontinuous sample stream will “chase” it, thereby forming a plateau onthe trailing edge of the first stage modulation pulse.

The plateau 34 falls to baseline sharply at 35, when the hot jet isturned off. At that moment, the cold jet once again falls onto themodulator stages, which begin accumulating chemical substances.Consequently, butane is removed from the carrier gas flow. The detectorregisters removal of butane from the carrier flow as a decrease in thebutane signal intensity, observed at 35 in FIG. 6. The butane signalintensity reached baseline in about 85 milliseconds, indicating thelength of time required to cool the first modulator stage to atemperature at which butane is fully retained (by this particularmodulator tube, which was uncoated) Clearly, the accumulation (cooling)profile observed at the edge of the plateau signal would permit detailedstudy of cooling and retention processes within a capillary tube.

Certain details of the modulation process apparent in FIG. 6 would notbe observable with any prior art thermal modulator. In all prior artdesigns, the spatial separation of the modulator stages was too small topermit temporal separation of the first stage chemical pulse from thesecond stage chemical pulse. With first and second chemical pulsesmerged in prior art devices, details of the thermal modulation processwere obscured. In particular, neither the terminal velocity nor therelease profile (a function of acceleration) of chemical pulses withinprior art thermal modulators could be directly determined, whereas thepresent invention facilitates such measurements.

Clearly, many variations of the present invention are possible withinthe scope of the above description. For example, multiple delay loopscan be passed through a jet structure, such as to produce dual column,dual detector chromatography. More than one jet structure can beemployed on a gas chromatograph. A cold jet can be pulsed by a valveinstead of operated continuously. A chemical pulse width can be measuredby varying the duration of the hot jet systematically, and monitoringthe growth of the first stage chemical pulse signal as a function of hotjet duration. Closed cycle refrigerators, rather than open cyclerefrigeration techniques, can be used with the loop modulator toeliminate consumption of cryogens. Many other variations can beenvisioned within the scope of the present invention.

Although the present invention has been described in connection withpreferred embodiments, it will be appreciated by those of skill in theart that additions, modifications, substitutions, and deletions notspecifically described may be made without departing from the spirit andscope of the invention defined in the appended claims.

1. A method of thermal modulation for generating chemical pulses in afluid stream flowing through a modulator tube, said method comprisingthe steps of: a. providing a modulator tube comprising an inlet, a firstportion in communication with said inlet, a second portion incommunication with said first portion, and an outlet portion incommunication with said second portion; b. creating a fluid stream in adirection through the modulator tube to produce a carrier fluid stream;c. introducing a sample into the carrier fluid stream, said samplecomprising one or more chemical substances; d. manipulating thetemperature of the first portion to cause at least a portion of thesample to be retained therein; e. manipulating the temperature of thesecond portion such that at least a portion of the sample will beretained therein; f. accumulating a sample component in the firstportion for a period of time to form a first concentration, theaccumulated sample component being carried into the first portion by thecarrier fluid stream; g. manipulating the temperature of the firstportion to release the first concentration into the carrier fluid streamin the form of a first chemical pulse; h. causing the first chemicalpulse to be carried in the direction of the carrier fluid stream flowtoward the second portion; i. accumulating the first chemical pulse insaid outlet portion so as to focus and hold the first chemical pulsetherein for a period of time and form a second concentration which ismore compact in distance than the first chemical pulse, samplecomponents of the first chemical pulse being carried to the outletportion by the carrier fluid stream; j. manipulating the temperature ofthe first portion to accumulate at least one second sample componenttherein for a period of time, the at least one second sample componentbeing carried into the first portion by the carrier fluid stream; k.manipulating the temperature of the second portion so as to release thesecond concentration into the carrier fluid stream in the form of anoutlet chemical pulse, the outlet chemical pulse being of shorterduration than the first chemical pulse; l. manipulating the temperatureof the second portion such that a subsequent chemical pulse is retainedtherein; and wherein travel of a first concentration from the firstportion to the second portion in step (h) is delayed such that: steps(d), (e), (j) and (l) occur simultaneously during an interval of time;and steps (g) and (k) occur simultaneously during an interval of time.2. The method of claim 1, wherein the modulator tube includes a portionthat is shaped in the form of a loop.
 3. A method according to claim 1,wherein steps (d), (e), (j), (l), (g), and (k) are effected within asingle thermal manipulation zone.
 4. A method according to claim 3,wherein a first portion and a second portion are formed by passing saidtube more than once through said single thermal manipulation zone, suchthat a delay loop between said first portion and said second portion isformed.
 5. A method according to claim 3, wherein said thermalmanipulation zone comprises a stream of cooled gas.
 6. A methodaccording to claim 5, wherein said stream of cooled gas is pulsed.
 7. Amethod according to claim 3, wherein said thermal manipulation zonecomprises a stream of heated gas.
 8. A method according to claim 7,wherein said stream of heated gas deflects a stream of cooled gas.
 9. Amethod according to claim 4 further comprising the steps of: m.measuring the time of travel of a concentration of a sample substancethrough said delay loop; n. measuring the length of said delay loop; ando. calculating the velocity of said concentration of sample substancethrough said delay loop.
 10. A method according to claim 9, furthercomprising determining a van't Hoff plot for a sample substance.
 11. Amethod according to claim 1, wherein said modulator tube is part of aone-dimensional gas chromatograph.
 12. A thermal modulation apparatusfor generating chemical pulses in a fluid stream flowing through amodulator tube, said apparatus comprising: a modulator tube having aninlet, a first portion which is a length of said tube in communicationwith said inlet, a second portion which is a length of said tube incommunication with said first portion, and an outlet portion incommunication with said second portion; a means for creating a fluidstream in a direction through said modulator tube to produce a carrierfluid stream; a means for introducing a sample comprising one or moresample components into the carrier fluid stream; a means formanipulating the temperature of the first portion to cause at least aportion of the sample to be retained therein; a means for manipulatingthe temperature of the second portion such that the one or morecomponents will be retained therein; a means for accumulating a samplecomponent in the first portion for a period of time to form a firstconcentration of sample, the accumulated sample substance being carriedinto the first portion by the carrier fluid stream; a means formanipulating the temperature of the first portion to release the firstconcentration into the carrier fluid stream in the form of a firstchemical pulse; a means for causing the first chemical pulse to becarried in the direction of carrier fluid stream flow toward the secondportion; a means for accumulating the first chemical pulse in saidoutlet portion so as to focus and hold the first chemical pulse thereinfor a period of time and form a second concentration of sample which ismore compact in distance than the first chemical pulse, samplesubstances of the first chemical pulse being carried to the outletportion by the carrier fluid stream; a means for manipulating thetemperature of the first portion to accumulate more sample substancetherein for a period of time, the sample substance being carried intothe first portion by the carrier fluid stream; a means for manipulatingthe temperature of the second portion so as to release the secondconcentration into the carrier flow stream in the form of an outletchemical pulse, the outlet chemical pulse being of shorter duration thanthe first chemical pulse; a means for manipulating the temperature ofthe second portion such that a subsequent chemical pulse is retainedtherein; and a means for delaying the travel of the first chemical pulseto the second portion, such that the temperatures of the first andsecond portions can be manipulated simultaneously.
 13. An apparatusaccording to claim 12, wherein said means for manipulating thetemperature of the first portion to release the first concentration intothe carrier fluid stream comprises a retention alteration means.
 14. Anapparatus according to claim 13, wherein said means for manipulating thetemperature of the first portion to release the first concentration intothe carrier fluid stream comprises a stream of heated gas directed ontothe first portion.
 15. The apparatus according to claim 12, wherein saidmeans for manipulating the temperature of the second portion to releasethe second concentration into the carrier fluid stream comprises aretention alteration means.
 16. The apparatus according to claim 15,wherein said means for manipulating the temperature of the secondportion to release the second concentration into the carrier fluidstream comprises a stream of heated gas directed onto the secondportion.
 17. The apparatus according to claim 12, said apparatus furthercomprising means for measuring the velocity of a chemical pulse betweenthe first portion and the second portion.
 18. The apparatus according toclaim 17, said apparatus further comprising means for constructing avan't Hoff plot.
 19. The apparatus according to claim 18, said apparatusfurther comprising means for predicting the velocity of a chemicalsubstance in a tube.
 20. The apparatus according to claim 12, forincreasing the sensitivity of a one-dimensional gas chromatograph. 21.The apparatus according to claim 12, wherein means for manipulating thetemperature of a first portion and a second portion comprise a singlepulsed stream of gas.
 22. The method of claim 1, wherein at least aportion of the modulator tube is formed in a loop such that the firstportion inlet and the second portion inlet are adjacent one another suchthat they are configured to be thermally modulated simultaneously with asingle thermal modulating device and the manipulating the temperature ofthe first portion and the manipulating the temperature of the secondportion comprise manipulating temperature with at least one thermalmodulating device adapted to direct at least one stream of heated gas,cooled gas, or both heated gas and cooled gas, toward said first andsecond portions simultaneously.
 23. A thermal modulation apparatus forgenerating chemical pulses in a fluid stream flowing through a modulatortube, said apparatus comprising: a modulator tube having an inlet, afirst portion in communication with said inlet, a second portion incommunication with said first portion, and an outlet portion incommunication with said second portion; a fluid stream in a directionthrough said modulator tube to produce a carrier fluid stream; aninjection port for introducing a sample comprising one or more samplecomponents into the carrier fluid stream; and a thermal modulator thatis adapted to: manipulate the temperature of the first portion to causeat least a portion of the sample to be retained therein; manipulate thetemperature of the second portion such that sample will be retainedtherein; accumulate a sample component in the first portion for a periodof time to form a first concentration of sample, the accumulated samplecomponent being carried into the first portion by the carrier fluidstream; manipulate the temperature of the first portion to release thefirst concentration into the carrier fluid stream in the form of a firstchemical pulse; cause the first chemical pulse to be carried in thedirection of carrier fluid stream flow toward the second portion;accumulate the first chemical pulse in said outlet portion so as tofocus and hold the first chemical pulse therein for a period of time andform a second concentration of sample which is more compact in distancethan the first chemical pulse, sample components of the first chemicalpulse being carried to the outlet portion by the carrier fluid stream;manipulate the temperature of the first portion to accumulate a secondsample component therein for a period of time, the second samplecomponent being carried into the first portion by the carrier fluidstream as an additional chemical pulse; manipulate the temperature ofthe second portion so as to release the second concentration into thecarrier flow stream in the form of an outlet chemical pulse, the outletchemical pulse being of shorter duration than the first chemical pulse;manipulate the temperature of the second portion such that a subsequentchemical pulse is retained therein; and delay the travel of the firstchemical pulse to the second portion, such that the temperatures of thefirst and second portions containing the additional chemical pulse andthe second chemical pulse, respectively, can be manipulatedsimultaneously.